Abstract
Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Masson's trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-β1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.
Highlights
Diabetes mellitus (DM) is a global health concern [1]
Compared with normal glucose (NG) and osmotic control (OC) treatments, High glucose (HG) (30 mM) treatment significantly increased the proliferation of Cardiac fibroblasts (CFs) in a time-dependent manner (P
HG-induced CF proliferation was markedly attenuated by neferine treatment at either 2 or 5 μM compared with vehicle treatment
Summary
The burden of diabetes as a major cause of premature illness and death is mostly due to the associated increased risk of cardiovascular disease, cardiac remodeling and heart failure. Cardiac fibrosis is reported to be a key pathogenic component of cardiovascular diseases [2]. Cardiac fibroblasts (CFs) are the predominant cell type in the heart, and are responsible for the basal deposition and degradation of the extracellular matrix (ECM) in the normal heart [4]. As the main matrix-producing cells, CFs are critically involved in all cardiac fibrotic conditions. High glucose (HG) in the blood (hyperglycemia), the main feature of diabetes mellitus, can stimulate collagen deposition by inducing CF proliferation and activation in vitro [5, 6]. On the basis of these concepts, inhibiting the activation of CFs could be a viable strategy for treating cardiac fibrosis
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